Acute and Chronic Effects of N-acetylcysteine on Pentylenetetrazole-induced Seizure and Neuromuscular Coordination in Mice

BACKGROUND N-acetylcysteine (NAC) has been indicated against experimental seizures, but with relatively inconclusive results. This study was undertaken to evaluate whether NAC exerts a dose-dependent anticonvulsant effect and to determine NAC safe therapeutic dose range and its muscle-relaxant activity in both acute and chronic uses. METHODS Following intraperitoneal (i.p.) administration of N-acetylcysteine acutely (50-300 mg/kg) or chronically for 8 days (25-300 mg/kg), mice were injected with PTZ (90 mg/kg, i.p.) and latency times to the onset of myoclonic and clonic seizures and protection against death were recorded. Changes in body weight and mortality rate were considered as parameters for drug safety. The muscle-relaxant activity of NAC was assessed by rotarod test. RESULTS Acute and chronic treatment with NAC delayed latency times to myoclonic and clonic seizures in a dose-dependent manner, but with no significant prevention against PTZ-induced death. Chronic administration of 300 mg/kg NAC was fully lethal while lower doses (100 and 150 mg/kg) resulted in a significant weight loss and decreased stay time on rotarod. Acute treatment with NAC had no significant effect on stay time on rotarod at all studied doses. CONCLUSION NAC exerts a dose-dependent anticonvulsant effect in acute and chronic uses, with no muscle relaxant activity. NAC has higher efficacy in preventing seizure in chronic than acute treatment, but its chronic use at higher doses of 75 mg/kg may be associated with side effects and/or toxicity. These findings suggest that low doses of NAC may have a potential use as a prophylactic treatment for absence seizure in human.